bims-ciryme 2023-01-15 papers

Curr Biol. 2022 Dec 29. pii: S0960-9822(22)01961-3. [Epub ahead of print]

Polyphasic circadian neural circuits drive differential activities in multiple downstream rhythmic centers.

Xitong Liang, Timothy E Holy, Paul H Taghert.

Circadian clocks align various behaviors such as locomotor activity, sleep/wake, feeding, and mating to times of day that are most adaptive. How rhythmic information in pacemaker circuits is translated to neuronal outputs is not well understood. Here, we used brain-wide, 24-h in vivo calcium imaging in the Drosophila brain and searched for circadian rhythmic activity among identified clusters of dopaminergic (DA) and peptidergic neurosecretory (NS) neurons. Such rhythms were widespread and imposed by the PERIOD-dependent clock activity within the ∼150-cell circadian pacemaker network. The rhythms displayed either a morning (M), evening (E), or mid-day (MD) phase. Different subgroups of circadian pacemakers imposed neural activity rhythms onto different downstream non-clock neurons. Outputs from the canonical M and E pacemakers converged to regulate DA-PPM3 and DA-PAL neurons. E pacemakers regulate the evening-active DA-PPL1 neurons. In addition to these canonical M and E oscillators, we present evidence for a third dedicated phase occurring at mid-day: the l-LNv pacemakers present the MD activity peak, and they regulate the MD-active DA-PPM1/2 neurons and three distinct NS cell types. Thus, the Drosophila circadian pacemaker network is a polyphasic rhythm generator. It presents dedicated M, E, and MD phases that are functionally transduced as neuronal outputs to organize diverse daily activity patterns in downstream circuits.

Keywords: Drosophila; GCaMP6; calcium; circadian physiology; dopamine; neuronal pacemakers; peptidergic

DOI: https://doi.org/10.1016/j.cub.2022.12.025

Acta Physiol (Oxf). 2023 Jan 10. e13928

The circadian neurobiology of reward.

Iwona Olejniczak, Kimberly Begemann, Ines Wilhelm, Henrik Oster.

Circadian clocks are important regulators of physiology and behaviour. In the brain, circadian clocks have been described in many centres of the central reward system. They affect neurotransmitter signalling, neuroendocrine circuits, and the sensitivity to external stimulation. Circadian disruption affects reward signalling, promoting the development of behavioral and substance use disorders. In this review we summarize our current knowledge of circadian clock-reward crosstalk. We show how chronodisruption affects reward signalling in different animal models. We then translate these findings to circadian aspects of human reward (dys-) function and its clinical implications. Finally, we devise approaches to and challenges in implementing the concepts of circadian medicine in the therapy of substance use disorders.

Keywords: chronomedicine; circadian clock; circadian disruption; neuronal centres; reward; substance use

DOI: https://doi.org/10.1111/apha.13928

Int J Environ Res Public Health. 2022 Dec 20. pii: 29. [Epub ahead of print]20(1):

Circadian Clock Desynchronization and Insulin Resistance.

Federica Catalano, Francesca De Vito, Velia Cassano, Teresa Vanessa Fiorentino, Angela Sciacqua, Marta Letizia Hribal.

The circadian rhythm regulates biological processes that occur within 24 h in living organisms. It plays a fundamental role in maintaining biological functions and responds to several inputs, including food intake, light/dark cycle, sleep/wake cycle, and physical activity. The circadian timing system comprises a central clock located in the suprachiasmatic nucleus (SCN) and tissue-specific clocks in peripheral tissues. Several studies show that the desynchronization of central and peripheral clocks is associated with an increased incidence of insulin resistance (IR) and related diseases. In this review, we discuss the current knowledge of molecular and cellular mechanisms underlying the impact of circadian clock dysregulation on insulin action. We focus our attention on two possible mediators of this interaction: the phosphatases belonging to the pleckstrin homology leucine-rich repeat protein phosphatase family (PHLPP) family and the deacetylase Sirtuin1. We believe that literature data, herein summarized, suggest that a thorough change of life habits, with the return to synchronized food intake, physical activity, and rest, would doubtless halt the vicious cycle linking IR to dysregulated circadian rhythms. However, since such a comprehensive change may be incompatible with the demand of modern society, clarifying the pathways involved may, nonetheless, contribute to the identification of therapeutic targets that may be exploited to cure or prevent IR-related diseases.

Keywords: circadian clock; insulin sensitivity; insulin signaling; peripheral tissues

DOI: https://doi.org/10.3390/ijerph20010029

Elife. 2023 01 10. pii: e79765. [Epub ahead of print]12

Adaptation to glucose starvation is associated with molecular reorganization of the circadian clock in Neurospora crassa.

Anita Szőke, Orsolya Sárkány, Géza Schermann, Orsolya Kapuy, Axel C R Diernfellner, Michael Brunner, Norbert Gyöngyösi, Krisztina Káldi.

The circadian clock governs rhythmic cellular functions by driving the expression of a substantial fraction of the genome and thereby significantly contributes to the adaptation to changing environmental conditions. Using the circadian model organism Neurospora crassa, we show that molecular timekeeping is robust even under severe limitation of carbon sources, however, stoichiometry, phosphorylation and subcellular distribution of the key clock components display drastic alterations. Protein kinase A, protein phosphatase 2 A and glycogen synthase kinase are involved in the molecular reorganization of the clock. RNA-seq analysis reveals that the transcriptomic response of metabolism to starvation is highly dependent on the positive clock component WC-1. Moreover, our molecular and phenotypic data indicate that a functional clock facilitates recovery from starvation. We suggest that the molecular clock is a flexible network that allows the organism to maintain rhythmic physiology and preserve fitness even under long-term nutritional stress.

Keywords: N. crassa; cell biology; chromosomes; circadian rhythm; gene expression; glucose starvation; neurospora; protein kinase A; protein phosphatase 2; transcriptome; white collar complex

DOI: https://doi.org/10.7554/eLife.79765

Nutrients. 2023 Jan 03. pii: 238. [Epub ahead of print]15(1):

Depot-Dependent Impact of Time-Restricted Feeding on Adipose Tissue Metabolism in High Fat Diet-Induced Obese Male Mice.

Theresa Bushman, Te-Yueh Lin, Xiaoli Chen.

Time-restricted feeding (TRF) is known to be an effective strategy for weight loss and metabolic health. TRF's effect on metabolism is complex and likely acts on various pathways within multiple tissues. Adipose tissue plays a key role in systemic homeostasis of glucose and lipid metabolism. Adipose tissue dysregulation has been causally associated with metabolic disorders in obesity. However, it is largely unknown how TRF impacts metabolic pathways such as lipolysis, lipogenesis, and thermogenesis within different in adipose tissue depots in obesity. To determine this, we conducted a 10-week TRF regimen in male mice, previously on a long-term high fat diet (HFD) and subjected the mice to TRF of a HFD for 10 h per day or ad libitum. The TRF regimen showed reduction in weight gain. TRF restored HFD-induced impairment of adipogenesis and increased lipid storage in white adipose tissues. TRF also showed a depot-dependent effect in lipid metabolism and restored ATP-consuming futile cycle of lipogenesis and lipolysis that is impaired by HFD within epididymal adipose tissue, but not inguinal fat depot. We demonstrate that TRF may be a beneficial option as a dietary and lifestyle intervention in lowering bodyweight and improving adipose tissue metabolism.

Keywords: adipose tissue; high-fat diet; metabolism; nutrition; obesity; time-restricted feeding

DOI: https://doi.org/10.3390/nu15010238